Fluorescence image analyzer and fluorescence image analyzing method

ABSTRACT

Disclosed is a fluorescence image analyzer for measuring and analyzing a sample that includes a plurality of cells in which target portions are labeled with fluorescent dyes, and the fluorescence image analyzer includes a light source configured to apply light to the sample; an imaging unit configured to take a fluorescence image of each of the cells by which fluorescence is generated by applying the light; a processing unit configured to process the fluorescence image having been taken; and a display unit. The processing unit obtains a bright point pattern of fluorescence in the fluorescence image, causes the display unit to display a plurality of positive patterns that are previously associated with at least one of a measurement item or a labeling reagent, and causes the display unit to display information of at least one of the number of abnormal cells included in the sample, a proportion of the number of the abnormal cells, the number of normal cells included in the sample, and a proportion of the normal cells, based on the bright point pattern having been obtained and the plurality of positive patterns.

RELATED APPLICATIONS

This application claims priority to Japanese Patent Application No.2019-065690, filed on Mar. 29, 2019, the entire content of which isincorporated herein by reference.

BACKGROUND OF THE INVENTION 1. Field of the Invention

The present invention relates to a fluorescence image analyzer and afluorescence image analyzing method.

2. Description of the Related Art

Japanese Patent Publication 2005-515408 discloses a cell processingmethod in which a flow cytometer or the like is applied to detection bya fluorescence in situ hybridization (FISH method). In the FISH method,a cell is stained in preprocessing in which a labeled probe ishybridized to a DNA sequence region to be detected in a cell.Fluorescence generated by the labeled probe is detected, therebydetecting an abnormal cell.

In the above-described analyzing method for analyzing an abnormal cell,positive patterns include typical positive patterns and atypicalpositive patterns. Furthermore, the atypical positive patterns may alsoinclude another positive pattern that occurs due to chromosomalabnormality such as deletion of a chromosome. An operator needs todetermine what positive pattern, among a plurality of positive patterns,corresponds to each cell in the sample without omission in order toaccurately determine whether the sample is positive or negative for acertain disease. Therefore, if a determination omission occurs in theabove-described analyzing method, accuracy for determining whether ornot each cell is abnormal may be degraded.

SUMMARY OF THE INVENTION

The scope of the present invention is defined solely by the appendedclaims, and is not affected to any degree by the statements within thissummary.

As shown in FIGS. 1, 3, 4A, 4B, and 7A to 7D, a fluorescence imageanalyzer (1) according to one aspect of the present invention isdirected to a fluorescence image analyzer for measuring and analyzing asample (10) that includes a plurality of cells in which target portionsare labeled with fluorescent dyes. The fluorescence image analyzerincludes a light source (120 to 123) configured to apply light to thesample (10); an imaging unit (160) configured to take a fluorescenceimage of each of the cells by which fluorescence is generated byapplying the light; a processing unit (11) configured to process thefluorescence image having been taken; and a display unit (13). Theprocessing unit (11) obtains a bright point pattern of fluorescence inthe fluorescence image, causes the display unit (13) to display aplurality of positive patterns that are previously associated with atleast one of a measurement item or a labeling reagent, and causes thedisplay unit (13) to display information of at least one of the numberof abnormal cells included in the sample (10), a proportion of thenumber of the abnormal cells, the number of normal cells included in thesample (10), or a proportion of the normal cells, based on the brightpoint pattern having been obtained and the plurality of positivepatterns.

According to the above-described aspect, the fluorescence image analyzer(1) obtains a bright point pattern of fluorescence in the fluorescenceimage, causes the display unit (13) to display a plurality of positivepatterns that are previously associated with at least one of ameasurement item or a labeling reagent, and causes the display unit (13)to display information of at least one of the number of abnormal cellsincluded in the sample (10), a proportion of the number of the abnormalcells, the number of normal cells included in the sample (10), or aproportion of the normal cells, based on the bright point pattern havingbeen obtained and the plurality of positive patterns. Therefore, whatpositive pattern, among a plurality of positive patterns, corresponds toa cell included in the sample (10) can be inhibited from beingundetermined. Accordingly, accuracy for determining whether the sample(10) is positive or negative can be improved. Furthermore, a user isallowed to easily recognize information of at least one of the number ofabnormal cells included in the sample (10), a proportion of the abnormalcells, the number of normal cells included in the sample (10), or aproportion of the normal cells.

As shown in FIGS. 1, 3, and 4A and 4B, in the fluorescence imageanalyzer (1), the processing unit (11) may cause the display unit (13)to display all of the plurality of positive patterns that are previouslyassociated with at least one of the measurement item or the labelingreagent such that the positive patterns can be selected.

According to the above-described aspect, the processing unit (11) causesthe display unit (13) to display all of the plurality of positivepatterns that are previously associated with at least one of themeasurement item or the labeling reagent such that the positive patternscan be selected. Therefore, what positive pattern, among a plurality ofpositive patterns, corresponds to a cell included in the sample 10 islikely to be inhibited from being undetermined. Accordingly, accuracyfor determining whether the sample 10 is positive or negative can befurther improved.

As shown in FIGS. 1, 3, and 4B, in the fluorescence image analyzer (1),the processing unit (11) may cause the display unit (13) to display theplurality of positive patterns that are previously associated with atleast one of the measurement item or the labeling reagent, and checkboxes located so as to correspond to the plurality of positive patterns,respectively.

According to the above-described aspect, the processing unit (11) causesthe display unit (13) to display the plurality of positive patterns thatare previously associated with at least one of the measurement item orthe labeling reagent, and check boxes located so as to correspond to theplurality of positive patterns, respectively. Therefore, each of theplurality of positive patterns that are previously associated with atleast one of the measurement item or the labeling reagent can beselected in a check box method. Accordingly, an operator is allowed toeasily perform an operation of selecting the positive pattern.

As shown in FIGS. 4A and 4B, in the fluorescence image analyzer (1), theprocessing unit (11) may manage, for each user, an authority to operatea selection screen that allows selection from among the plurality ofpositive patterns, and may cause the display unit (13) to display theselection screen corresponding to a specific user having the authority.

According to the above-described aspect, the processing unit (11)manages, for each user, an authority to operate a selection screen thatallows selection from among the plurality of positive patterns, andcauses the display unit (13) to display the selection screencorresponding to a specific user having the authority. Therefore, theauthorized specific user is allowed to operate the selection screencorresponding to the specific user. Accordingly, another user can beprohibited from operating the selection screen and changing the positivepattern which has been desirably set by the specific user withoutpermission.

As shown in FIGS. 1 and 9 , the fluorescence image analyzer (1) mayfurther include a storage unit (12) configured to store determinationresults for the sample (10), and the processing unit (11) may cause thedisplay unit (13) to display all the determination results having beenstored.

According to the above-described aspect, the processing unit (11) causesthe display unit (13) to display all the determination results havingbeen stored. What positive pattern, among a plurality of positivepatterns, corresponds to a cell included in the sample 10 can be likelyto be inhibited from being undetermined. Accordingly, accuracy fordetermining whether the sample 10 is positive or negative can be furtherimproved.

As shown in FIGS. 9 and 10 , in the fluorescence image analyzer (1), theprocessing unit (11) may cause the display unit (13) to displayinformation of at least one of the number of the abnormal cells includedin the sample (10), a proportion of the abnormal cells, the number ofthe normal cells included in the sample (10), or a proportion of thenormal cells, together with fluorescence images of cells included in thesample (10).

According to the above-described aspect, the processing unit (11) causesthe display unit (13) to display the information of at least one of thenumber of abnormal cells included in the sample (10), a proportion ofthe abnormal cells, the number of normal cells included in the sample(10), or a proportion of the normal cells, together with fluorescenceimages of cells included in the sample (10). Therefore, a user isallowed to confirm information of at least one of the number of abnormalcells included in the sample (10), the proportion of the abnormal cells,the number of normal cells included in the sample (10), or theproportion of the normal cells, together with the fluorescence images ofthe cells included in the sample (10).

As shown in FIGS. 9 and 10 , in the fluorescence image analyzer (1), theprocessing unit (11) may cause the display unit (13) to display a graphimage indicating at least one of a proportion of the abnormal cellsincluded in the sample (10) or a proportion of the normal cells includedin the sample (10), together with text information indicating at leastone of the proportion of the abnormal cells or the proportion of thenormal cells.

According to the above-described aspect, the processing unit (11) causesthe display unit (13) to display a graph image indicating at least oneof a proportion of abnormal cells included in the sample (10) or aproportion of normal cells included in the sample (10), together withtext information indicating at least one of the proportion of theabnormal cells or the proportion of the normal cells. Therefore, a useris allowed to confirm the text information indicating at least one ofthe proportion of abnormal cells included in the sample (10) or theproportion of normal cells included in the sample (10), together withthe graph image.

As shown in FIGS. 9 and 10 , in the fluorescence image analyzer (1), theprocessing unit (11) may cause the display unit (13) to display adetermination result regarding a positive pattern for which the numberof the abnormal cells included in the sample (10) is greatest, or aproportion of the abnormal cells included in the sample (10) isgreatest, in a display manner different from that for a determinationresult regarding another positive pattern.

According to the above-described aspect, the processing unit (11) causesthe display unit (13) to display the determination result regarding apositive pattern for which the number of abnormal cells included in thesample (10) is greatest, or the proportion of abnormal cells included inthe sample (10) is greatest, in a display manner different from that forthe determination result regarding another positive pattern. Therefore,a user is allowed to more easily recognize the determination resultregarding the positive pattern for which the number of abnormal cells orthe proportion of abnormal cells is greatest, on the determinationresult screen including various determination results.

As shown in FIGS. 7A to 7D, in the fluorescence image analyzer (1), theplurality of positive patterns that are previously associated with atleast one of the measurement item or the labeling reagent may bedetermined based on colors and the number of bright points offlorescence generated from the fluorescent dyes with which the targetportions are labelled.

As shown in FIGS. 1, 3, 4A, 4B, and 7A to 7D, a fluorescence imageanalyzing method according to one aspect of the present invention isdirected to a fluorescence image analyzing method for measuring andanalyzing a sample (10) that includes a plurality of cells in whichtarget portions are labeled with fluorescent dyes. The fluorescenceimage analyzing method includes taking a fluorescence image of each ofthe cells by which fluorescence is generated by light being applied tothe sample (10) from a light source; and processing the fluorescenceimage having been taken. The processing includes obtaining a brightpoint pattern of fluorescence in the fluorescence image, causing adisplay unit (13) to display a plurality of positive patterns that arepreviously associated with at least one of a measurement item or alabeling reagent, and causing the display unit (13) to displayinformation of at least one of the number of abnormal cells included inthe sample (10), a proportion of the number of the abnormal cells, thenumber of normal cells included in the sample (10), or a proportion ofthe normal cells, based on the bright point pattern having been obtainedand the plurality of positive patterns.

According to the above-described aspect, the processing includesobtaining a bright point pattern of fluorescence in the fluorescenceimage; causing the display unit (13) to display a plurality of positivepatterns that are previously associated with at least one of ameasurement item or a labeling reagent; and causing the display unit(13) to display information of at least one of the number of abnormalcells included in the sample (10), a proportion of the number of theabnormal cells, the number of normal cells included in the sample (10),or a proportion of the normal cells, based on the bright point patternhaving been obtained and the plurality of positive patterns. Therefore,what positive pattern, among a plurality of positive patterns,corresponds to a cell included in the sample (10) can be inhibited frombeing undetermined. Accordingly, accuracy for determining whether thesample (10) is positive or negative can be improved. Furthermore, a useris allowed to easily recognize information of at least one of the numberof abnormal cells included in the sample (10), a proportion of theabnormal cells, the number of normal cells included in the sample (10),or a proportion of the normal cells.

As shown in FIGS. 1, 3, and 4A and 4B, in the fluorescence imageanalyzing method, the processing may include causing the display unit(13) to display all of the plurality of positive patterns that arepreviously associated with at least one of the measurement item or thelabeling reagent such that the positive patterns can be selected.

According to the above-described aspect, in the processing, the displayunit (13) is caused to display all of the plurality of positive patternsthat are previously associated with at least one of the measurement itemor the labeling reagent such that the positive patterns can be selected.Therefore, what positive pattern, among a plurality of positivepatterns, corresponds to a cell included in the sample 10 is likely tobe inhibited from being undetermined. Thus, accuracy for determiningwhether the sample 10 is positive or negative can be further improved.

As shown in FIGS. 1, 3, and 4B, in the fluorescence image analyzingmethod, the processing may include causing the display unit (13) todisplay the plurality of positive patterns that are previouslyassociated with at least one of the measurement item or the labelingreagent, and check boxes located so as to correspond to the plurality ofpositive patterns, respectively.

According to the above-described aspect, in the processing, the displayunit (13) is caused to display the plurality of positive patterns thatare previously associated with at least one of the measurement item orthe labeling reagent, and check boxes located so as to correspond to theplurality of positive patterns, respectively. Therefore, each of theplurality of positive patterns that are previously associated with atleast one of the measurement item or the labeling reagent can beselected in a check box method. Accordingly, an operator is allowed toeasily perform an operation of selecting the positive pattern.

As shown in FIGS. 4A and 4B, in the fluorescence image analyzing method,the processing may include managing, for each user, an authority tooperate a selection screen that allows selection from among theplurality of positive patterns; and causing the display unit (13) todisplay the selection screen corresponding to a specific user having theauthority.

According to the above-described aspect, in the processing, an authorityto operate a selection screen that allows selection from among theplurality of positive patterns is managed for each user, and the displayunit (13) is caused to display the selection screen corresponding to aspecific user having the authority. Therefore, the authorized specificuser is allowed to operate the selection screen corresponding to thespecific user. Accordingly, another user can be prohibited fromoperating the selection screen and changing the positive pattern whichhas been desirably set by the specific user without permission.

As shown in FIGS. 1, 9 and 11 , the fluorescence image analyzing methodmay further include storing determination results for the sample (10),and the processing may include causing the display unit (13) to displayall the determination results having been stored.

According to the above-described aspect, in the processing, the displayunit (13) is caused to display all the determination results having beenstored. What positive pattern, among a plurality of positive patterns,corresponds to a cell included in the sample (10) can be likely to beinhibited from being undetermined. Accordingly, accuracy for determiningwhether the sample (10) is positive or negative can be further improved.

As shown in FIGS. 9 to 11 , in the fluorescence image analyzing method,the processing may include causing the display unit (13) to displayinformation of at least one of the number of the abnormal cells includedin the sample, a proportion of the abnormal cells, the number of thenormal cells included in the sample (10), or a proportion of the normalcells, together with fluorescence images of cells included in the sample(10).

According to the above-described aspect, in the processing, the displayunit (13) is caused to display the information of at least one of thenumber of abnormal cells included in the sample (10), a proportion ofthe abnormal cells, the number of normal cells included in the sample(10), or a proportion of the normal cells, together with fluorescenceimages of cells included in the sample (10). Therefore, a user isallowed to confirm information of at least one of the number of abnormalcells included in the sample (10), the proportion of the abnormal cells,the number of normal cells included in the sample (10), or theproportion of the normal cells, together with the fluorescence images ofthe cells included in the sample (10).

As shown in FIGS. 9 to 11 , in the fluorescence image analyzing method,the processing may include causing the display unit (13) to display agraph image indicating at least one of a proportion of the abnormalcells included in the sample (10) or a proportion of the normal cellsincluded in the sample (10), together with text information indicatingat least one of the proportion of the abnormal cells or the proportionof the normal cells.

According to the above-described aspect, in the processing, the displayunit (13) is caused to display a graph image indicating at least one ofa proportion of abnormal cells included in the sample (10) or aproportion of normal cells included in the sample (10), together withtext information indicating at least one of the proportion of theabnormal cells or the proportion of the normal cells. Therefore, a useris allowed to confirm the text information indicating at least one ofthe proportion of abnormal cells included in the sample (10) or theproportion of normal cells included in the sample (10), together withthe graph image.

As shown in FIGS. 9 to 11 , in the fluorescence image analyzing method,the processing may include causing the display unit (13) to display adetermination result regarding a positive pattern for which the numberof the abnormal cells included in the sample (10) is greatest, or aproportion of the abnormal cells included in the sample (10) isgreatest, in a display manner different from that for a determinationresult regarding another positive pattern.

According to the above-described aspect, in the processing, the displayunit (13) is caused to display the determination result regarding apositive pattern for which the number of abnormal cells included in thesample (10) is greatest, or the proportion of abnormal cells included inthe sample (10) is greatest, in a display manner different from that forthe determination result regarding another positive pattern. Therefore,a user is allowed to more easily recognize the determination resultregarding the positive pattern for which the number of abnormal cells orthe proportion of abnormal cells is greatest, on the determinationresult screen including various determination results.

As shown in FIGS. 7A to 7B, in the fluorescence image analyzing method,the plurality of positive patterns that are previously associated withat least one of the measurement item or the labeling reagent may bedetermined based on colors and the number of bright points offlorescence generated from the fluorescent dyes with which the targetportions are labelled.

According to the present invention, accuracy for determining whether asample is positive or negative can be improved.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of one example of configurations of afluorescence image analyzer and a preprocessing device according to anembodiment;

FIG. 2A illustrates first to third images and a bright field image whichare obtained by the fluorescence image analyzer according to theembodiment;

FIG. 2B illustrates extraction, of a region of a nucleus, performed bythe fluorescence image analyzer according to the embodiment;

FIGS. 2C and 2D each illustrate extraction, of a region of a brightpoint, performed by the fluorescence image analyzer according to theembodiment;

FIG. 3 illustrates one example of a functional block configuration of aprocessing unit of the fluorescence image analyzer according to theembodiment;

FIG. 4A illustrates one example of a specifying screen for specifying ameasurement item and a labeling reagent in a display unit of thefluorescence image analyzer according to the embodiment;

FIG. 4B illustrates one example of a positive pattern selection screenin the display unit of the fluorescence image analyzer according to theembodiment;

FIG. 5A illustrates one example of a reading process of reading a codeon a storage box in which a labeling reagent is stored, with the use ofa reading unit according to the embodiment;

FIG. 5B illustrates one example of a reading process of reading a codeon an attached document regarding the labeling reagent, with the use ofa reading unit according to the embodiment;

FIG. 6 illustrates one example of a registration screen for registeringinformation regarding a bright point pattern in the display unit of thefluorescence image analyzer according to the embodiment;

FIGS. 7A to 7D schematically illustrate examples of arrangements ofbright points in a negative pattern, a positive pattern 1, a positivepattern 2, and a positive pattern 3, respectively, according to theembodiment;

FIG. 8A and FIG. 8B each illustrate an example of target portions to behybridized to a probe of which the target is a BCR/ABL fusion geneaccording to the embodiment;

FIG. 9 illustrates one example of a determination result screen in thedisplay unit of the fluorescence image analyzer according to theembodiment;

FIG. 10 is an enlarged view of a part of the determination result screenshown in FIG. 9 ;

FIG. 11 is a flow chart showing one example of an operation performed bythe processing unit of the fluorescence image analyzer, according to theembodiment;

FIG. 12 is a flow chart showing one example of a process performed bythe processing unit of the fluorescence image analyzer for obtaining abright point pattern, according to the embodiment;

FIG. 13 is a flow chart showing one example of a process performed bythe processing unit of the fluorescence image analyzer for selecting abright point pattern, according to the embodiment;

FIG. 14 is a flow chart showing one example of a determination processperformed by the processing unit of the fluorescence image analyzer,according to the embodiment;

FIG. 15 is a flow chart showing another example of the determinationprocess performed by the processing unit of the fluorescence imageanalyzer, according to the embodiment; and

FIG. 16 is a flow chart showing one example of a display control processperformed by the processing unit of the fluorescence image analyzer,according to the embodiment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A preferable embodiment of the present disclosure will be describedbelow with reference to the drawings. The same components are denoted bythe same reference characters, and repeated description thereof isomitted. Unless otherwise specified, the positional relationship amongupper, lower, left, right, and the like are based on the positionalrelationship shown in the drawings. Furthermore, the dimensionalproportions in the drawings are not limited to the proportions showntherein. The embodiment described below is illustrative merely fordescribing the present disclosure, and the present disclosure is notlimited to the embodiment.

The present disclosure is applied to an apparatus for measuring andanalyzing a sample prepared in preprocessing that includes hybridizing anucleic acid probe labeled with a fluorescent dye, with a target portionin a nucleic acid, as the embodiment described below. Specifically, inthe embodiment described below, the target portions in the nucleic acidare BCR gene on chromosome 22 and ABL gene on chromosome 9, and a cellin which translocation occurs between chromosome 9 and chromosome 22 asis observed in chronic myeloid leukemia is detected as an abnormal cellbased on the FISH method. That is, in the embodiment described below,for example, a cell in which BCR-ABL fusion gene is generated due to thetranslocation of BCR gene or ABL gene is detected as the abnormal cell.

FIG. 1 illustrates a schematic configuration of a fluorescence imageanalyzer 1 according to the present embodiment. The fluorescence imageanalyzer 1 shown in FIG. 1 includes, for example, a measurement device100 and a processing device 200, and measures and analyzes a sample 10prepared in the preprocessing by a preprocessing device 300. An operator(user) collects nucleated cells that are cells to be measured by, forexample, centrifuging a blood specimen collected from a subject with theuse of, for example, a cell separation medium such as Ficoll. When thenucleated cells are collected, red blood cells or the like may behemolyzed by using a hemolyzing agent to leave nucleated cells insteadof the nucleated cells being collected by centrifugation.

The preprocessing device 300 includes, for example, a mixing containerin which a reagent and a nucleated cell suspension obtained bycentrifugation or the like are mixed, a dispensing unit for dispensingthe nucleated cell suspension and the reagent into the mixing container,and a heating unit for heating the mixing container. The preprocessingdevice 300 prepares the sample 10 in preprocessing that includes, forexample, labeling the target portion in the cell collected from asubject, with a fluorescent dye, and staining the nucleus in the cell bya nucleus staining dye. Specifically, in labeling the target portionwith a fluorescent dye, a target sequence is hybridized to a probe thatis labeled with a fluorescent dye and that includes a nucleic acidsequence having a sequence complementary to the target sequence.

In the FISH method, the target portions on chromosomes are detected byusing one or more fluorescent dyes. Preferably, in the FISH method, atarget portion on a first chromosome and a target portion on a secondchromosome are detected by using two or more fluorescent dyes (“first”and “second” that modify “chromosome” do not represent chromosomenumbers but represent a comprehensive numerical concept). For example, aprobe to be hybridized with BCR gene locus is formed such that a nucleicacid having a sequence complementary to a base sequence in the BCR genelocus is labeled with a first fluorescent dye that generates a firstfluorescence having a wavelength λ21 by light having a wavelength λ11being applied. By using this probe, the BCR gene locus is labeled withthe first fluorescent dye. A probe to be hybridized with ABL gene locusis formed such that a nucleic acid having a sequence complementary to abase sequence in the ABL gene locus is labeled with a second fluorescentdye that generates a second fluorescence having a wavelength λ22 bylight having a wavelength λ12 being applied. By using this probe, theABL gene locus is labeled with the second fluorescent dye. The nucleusis stained by a nucleus staining dye that generates a third fluorescencehaving a wavelength λ23 by light having a wavelength λ13 being applied.Light having the wavelength λ11, light having the wavelength λ12, andlight having the wavelength λ13 are each so-called excitation light.

Specifically, the preprocessing device 300 performs, for example, aprocess of fixing a cell such that the cell does not contract bydehydration, a membrane permeating process of forming, in a cell, a holehaving such a size as to introduce the probe into the cell, a thermaldenaturing process of heating a cell, a process of hybridizing a probewith a target portion, a washing process of removing an unnecessaryprobe from the cell, and a process of staining a nucleus.

The measurement device 100 includes, for example, a flow cell 110, lightsources 120 to 123, condenser lenses 130 to 133, dichroic mirrors 140 to141, a condenser lens 150, an optical unit 151, a condenser lens 152,and an imaging unit 160. The sample 10 flows through a flow path 111 ofthe flow cell 110.

The light sources 120 to 123 apply light to the sample 10 that flowsthrough the flow cell 110. The light sources 120 to 123 are eachimplemented by, for example, a semiconductor laser light source. Thelight sources 120 to 123 emit lights having the wavelengths λ11 to λ14,respectively.

The condenser lenses 130 to 133 condense lights, having the wavelengthsλ11 to λ14, which are emitted from the light sources 120 to 123,respectively. The dichroic mirror 140 allows the light having thewavelength λ11 to be transmitted therethrough and refracts the lighthaving the wavelength λ12. The dichroic mirror 141 allows the lightshaving the wavelengths λ11 and λ12 to be transmitted therethrough andrefracts the light having the wavelength λ13. Thus, the lights havingthe wavelengths λ11 to λ14 are applied to the sample 10 that flowsthrough the flow path 111 of the flow cell 110. The number of thesemiconductor laser light sources included in the measurement device 100is not particularly limited as long as the number of the semiconductorlaser light sources is not less than one. The number of thesemiconductor laser light sources can be selected from among, forexample, 1, 2, 3, 4, 5, and 6.

When the lights having the wavelengths λ11 to λ13 are applied to thesample 10 that flows through the flow cell 110, fluorescences aregenerated from fluorescent dyes by which the cell is stained. Forexample, when the light having the wavelength λ11 is applied to thefirst fluorescent dye with which the BCR gene locus is labeled, thefirst fluorescence having the wavelength λ21 is generated from the firstfluorescent dye. When the light having the wavelength λ12 is applied tothe second fluorescent dye with which the ABL gene locus is labeled, thesecond fluorescence having the wavelength λ22 is generated from thesecond fluorescent dye. When the light having the wavelength λ13 isapplied to the nucleus staining dye by which the nucleus is stained, thethird fluorescence having the wavelength λ23 is generated from thenucleus staining dye. When the light having the wavelength λ14 isapplied to the sample 10 that flows through the flow cell 110, the lightis transmitted through the cell. The light, having the wavelength λ14,which has been transmitted through the cell is used for generating abright field image. For example, in the embodiment, the firstfluorescence is in a wavelength band of green light, the secondfluorescence is in a wavelength band of red light, and the thirdfluorescence is in a wavelength band of blue light.

The condenser lens 150 condenses the first fluorescence to the thirdfluorescence that are generated from the sample 10 flowing through theflow path 111 of the flow cell 110, and the transmitted light that hasbeen transmitted through the sample 10 flowing through the flow path 111of the flow cell 110. The optical unit 151 includes four dichroicmirrors combined with each other. The four dichroic mirrors of theoptical unit 151 reflect the first fluorescence to the thirdfluorescence and the transmitted light at slightly different angles,respectively, to separate them on a light receiving surface of theimaging unit 160. The condenser lens 152 condenses the firstfluorescence to the third fluorescence and the transmitted light.

The imaging unit 160 is implemented by a TDI (Time Delay Integration)camera. The imaging unit 160 takes images of the first fluorescence tothe third fluorescence and the transmitted light, and outputsfluorescence images corresponding to the first fluorescence to the thirdfluorescence and a bright field image corresponding to the transmittedlight, as image pickup signals, to the processing device 200.Hereinafter, the fluorescence images corresponding to the firstfluorescence to the third fluorescence are referred to as “first image”,“second image”, and “third image”, respectively. The “first image”, the“second image”, and the “third image” preferably have the same size inorder to analyze overlapping of bright points. The “first image”, the“second image”, and the “third image” may be color images or gray scaleimages.

In the present embodiment, the bright point represents a small point offluorescence generated in the fluorescence image. More specifically, thebright point represents a point of fluorescence generated from afluorescent dye of a nucleic acid probe that binds to a gene which is atarget portion in a nucleus.

FIG. 2A illustrates the first to the third images and the bright fieldimage which are obtained by the fluorescence image analyzer according tothe embodiment. In FIG. 2A, dot-like black portions in the first imagerepresent bright points of the first fluorescence, that is, targetportions labeled with the first fluorescent dye. In the second image,dark gray points are observed, less clearly than in the first image, ina light gray portion that represents a nucleus. These represent brightpoints of the second fluorescence, that is, the target portions labeledwith the second fluorescent dye. In the third image, an almost roundnucleus region is indicated in black. In the bright field image, anactual state of the cell can be observed. Each of the images shown inFIG. 2A represents, as an example, a preprocessed white blood cell, on aglass slide, which is observed by a microscope. The fluorescence imageis taken such that, in raw data, the higher the intensity of thefluorescence is, the paler the image is, and the lower the intensity ofthe fluorescence is, the darker the image is. In the first to the thirdimages shown in FIG. 2A, the gradation in the raw data of the takenimage is inverted and the first to the third images are represented asgray scale images. When an image of the sample 10 flowing in the flowcell 110 is taken by the imaging unit 160 as described above, thefluorescence images and the bright field image are obtained for eachcell since the cells are separated from each other in the flow path 111and flow therein.

Returning to FIG. 1 , the processing device 200 has a hardwareconfiguration that includes, for example, a processing unit 11, astorage unit 12, a display unit 13, and an input unit 14. The processingunit 11 is implemented by a processor (CPU). The storage unit 12 isimplemented by, for example, a memory (RAM) into and from which data canbe written and read, and which is used as a work area for variousprocesses performed by the processing unit 11, a read-only-memory (ROM)for storing computer programs and data, and a hard disk. The processingunit 11 and the storage unit 12 can be each implemented by ageneral-purpose computer. The hard disk may be included in the computeror may be an external device outside the computer. The display unit 13is implemented by, for example, a display. The input unit 14 isimplemented by, for example, a mouse, a keyboard, and a touch paneldevice. The processing unit 11 performs data transmission with thestorage unit 12 via a bus 15, and performs data input and output withthe display unit 13, the input unit 14, and the measurement device 100via an interface 16.

For example, the processing unit 11 reads, into the RAM, variouscomputer programs stored in the ROM or the hard disk and executes thecomputer programs, to process the fluorescence image of the cell whichhas been obtained by the sample 10 being measured by the measurementdevice 100 and to control operations of the display unit 13, the inputunit 14, and the like.

FIG. 3 illustrates one example of a block configuration of theprocessing unit 11 of the fluorescence image analyzer 1 according to theembodiment. As shown in FIG. 3 , the processing unit 11 functionallyincludes an obtaining unit 21, a selection unit 23, a determination unit25, and a display control unit 27.

For example, the obtaining unit 21 obtains the first to the third imagesby inverting gradation of the raw data of the images taken by theimaging unit 160 and displaying the images as gray scale images. Theobtaining unit 21 stores the obtained first to third images in thestorage unit 12.

The obtaining unit 21 obtains a bright point pattern of fluorescence inthe fluorescence image. For example, the obtaining unit 21 obtains abright point pattern of the first fluorescence in the first image basedon the first fluorescence, and a bright point pattern of the secondfluorescence in the second image based on the second fluorescence.

Returning to FIG. 2 , FIG. 2B illustrates extraction, of a region of anucleus, performed by the fluorescence image analyzer according to theembodiment. FIGS. 2C and 2D each illustrate extraction, of a region of abright point, performed by the fluorescence image analyzer according tothe embodiment. The third image shown at the left end in FIG. 2B, thefirst image shown at the left end in FIG. 2C, and the second image shownat the left end in FIG. 2D are obtained from the same region of thesample 10 that flows through the flow cell 110 shown in FIG. 1 .

When the third image is obtained as shown at the left end in FIG. 2B,the obtaining unit 21 generates a graph of brightness against frequencybased on the brightness in each pixel in the third image as shown at thecenter in FIG. 2B. The frequency on the vertical axis represents thenumber of pixels. The obtaining unit 21 sets a threshold value of thebrightness in the graph. The obtaining unit 21 extracts, as a region ofa nucleus, a range in which pixels each having a brightness higher thanthe threshold value are distributed, as indicated by broken lines at theright end in FIG. 2B. When two nuclei overlap each other in the thirdimage, the first to the third images for the overlapping cells are notused for determining whether or not the preprocessing is appropriate andwhether or not the cell is an abnormal cell, and are excluded.

When the first image is obtained as shown at the left end in FIG. 2C,the obtaining unit 21 generates a graph of brightness against frequencybased on the brightness in each pixel in the first image as shown at thecenter of FIG. 2C. The obtaining unit 21 sets a threshold value of thebrightness for a boundary between a bright point and a background in thegraph based on, for example, the Otsu method. The obtaining unit 21extracts, as a region of a bright point, a range in which pixels eachhaving a brightness higher than the threshold value are distributed, asindicated by broken lines at the right end in FIG. 2C. When the regionof the bright point is extracted from the first image, a bright point ofan extremely small region, a bright point of an extremely large region,and a bright point which is not included in the region of the nucleus asshown at the right end in FIG. 2B are excluded.

When the second image is obtained as shown at the left end in FIG. 2D,the obtaining unit 21 generates a graph of brightness against frequencybased on the brightness in each pixel in the second image as shown atthe center in FIG. 2D, similarly to the first image. The obtaining unit21 sets a threshold value of brightness in the graph and extracts, as aregion of a bright point, a range in which pixels each having abrightness higher than the threshold value are distributed, as indicatedby broken lines at the right end in FIG. 2D. When the region of thebright point is extracted from the second image, a bright point of anextremely small region, a bright point of an extremely large region, anda bright point which is not included in the region of the nucleus asshown at the right end in FIG. 2B are excluded.

The obtaining unit 21 may extract the region of the nucleus from thethird image and extract the regions of the bright points from brightpoints in the first image and the second image by calculation accordingto the above-described procedure without generating the graph as shownat the center in each of FIGS. 2B to 2D. In extracting the bright point,a degree of matching between a region to be determined and a normaldistribution waveform of the bright point may be determined. In thiscase, when the degree of the matching is high, the region to bedetermined may be extracted as the bright point. The obtaining unit 21extracts the region of the nucleus from the third image, to detect acell. However, the obtaining unit 21 may detect a cell based on thebright field image. When the cell is detected based on the bright fieldimage, obtaining of the third image may be omitted.

Returning to FIG. 3 , the selection unit 23 of the processing unit 11selects, according to an instruction from an operator, at least onebright point pattern from among a plurality of bright point patternsthat include one or more positive patterns and are previously associatedwith at least one of a measurement item or a labeling reagent. Oneexample of the selection process of selecting a bright point patternwill be described below. For example, the processing unit 11 performs aprocess of selecting at least one bright point pattern associated withat least one of the measurement item or the labeling reagent for asample, from among a plurality of bright point patterns which are storedin the storage unit 12 and associated with at least one of pluralmeasurement items or plural labeling reagents.

FIG. 4A illustrates one example of a specifying screen SC1 forspecifying a measurement item and a labeling reagent, on the displayunit 13, according to the embodiment. As shown in FIG. 4A, on thespecifying screen SC1, for example, an item “measurement item” or anitem “probe name” (labeling reagent) can be specified by a drop-downmenu method. For the “measurement item”, for example, BCR/ABL fusiongene, ALK gene, deletion of the long arm of chromosome 5, or the likecan be selected for each cell. For the “probe name”, for example, whenthe “measurement item” is BCR/ABL fusion gene, the DF probe, the ESprobe, or the like can be selected. The DF probe and the ES probe forBCR/ABL fusion gene and the like will be described below in detail.

The processing unit 11 causes the display unit 13 to display, to anoperator, the specifying screen SC1 for specifying the measurement itemand the labeling reagent for the sample 10 such that the contents of themeasurement item can be specified more preferentially than the contentsof the labeling reagent. For example, the processing unit 11 may performcontrol so as to display the item “measurement item” at a higher orderthan the item “probe name” in the specifying screen SC1, as shown inFIG. 4A. The processing unit 11 may perform display so as to highlightonly the item “measurement item” in the specifying screen SC1. Moreover,the processing unit 11 may perform control such that, after the item“measurement item” is specified in the specifying screen SC1, the item“probe name” corresponding to the contents of the specified item,“measurement item”, can be specified. The processing unit 11 may operateto initially display a specifying screen including the item “measurementitem”, and display a specifying screen, including the item “probe name”,which is different from the specifying screen including the item“measurement item” after the “measurement item” has been specified, inorder to allow an operator to specify the contents of the measurementitem more preferentially than the contents of the labeling reagent. Inthis case, the processing unit 11 may perform control so as not todisplay the specifying screen including the “measurement item” whendisplaying the specifying screen including the item “probe name”.

In the above-described configuration, the operator is allowed to specifythe contents of the measurement item more preferentially than thecontents of the labeling reagent. Therefore, after the bright pointpatterns associated with the measurement items have been narrowed, thebright point patterns associated with the labeling reagent can befurther specified. Accordingly, the bright point pattern can beefficiently selected.

FIG. 4B illustrates one example of a positive pattern selection screenSC3 on the display unit 13 according to the embodiment. As shown in FIG.4B, the processing unit 11 causes the display unit 13 to display all ofone or more positive patterns that are previously associated with atleast one of the measurement item or the labeling reagent such that thepositive patterns can be selected. For example, when the operatorspecifies a measurement item “BCR-ABL” and a probe name “ES” in thespecifying screen SC1 shown in FIG. 4A, the positive pattern selectionscreen SC3 shown in FIG. 4B is displayed on the display unit 13 shown inFIG. 1 . In this example, the positive patterns that are included in theplurality of positive patterns stored in the storage unit 12 shown inFIG. 1 and associated with the measurement item “BCR-ABL” and the probename “ES” are “typical pattern G1R2F1”, “minor pattern G1R1F2”, “9qdeletion pattern G2R1F1”, and “9q⋅22q deletion pattern G1R1F1” which areshown in FIG. 4B. Therefore, check boxes of the patterns in FIG. 4B areall checked. That is, all the positive patterns for which thedetermination results are to be displayed are selected. However, forexample, when the operator operates the positive pattern selectionscreen SC3 to uncheck one or more of the check boxes, at least onepositive pattern can be excluded from the positive patterns for whichthe determination results are to be displayed. Meanwhile, even if apositive pattern is excluded from the positive patterns for which thedetermination results are to be displayed, when the operator operatesthe positive pattern selection screen SC3 to press a “display allpositive patterns” button BT, all of the check boxes corresponding to“typical pattern G1R2F1”, “minor pattern G1R1F2”, “9q deletion patternG2R1F1”, and “9q⋅22q deletion pattern G1R1F1” may be checked. Thepositive pattern selection screen SC3 may further include a button, forunchecking all the positive patterns, such as a “non-display of allpositive patterns” button, which is not shown.

Only the positive patterns are displayed on the positive patternselection screen SC3 shown in FIG. 4B. However, the positive patternselection screen SC3 may include negative patterns associated with themeasurement item “BDR-ABL” and the probe name “ES”. That is, theprocessing unit 11 may operate to display a screen including brightpoint patterns that include positive patterns and negative patternsassociated with the specified measurement item and probe name.

The processing unit 11 may change, according to an instruction from anoperator, at least one of the selected bright point patterns. Forexample, the processing unit 11 may cause the display unit 13 to displaythe positive pattern selection screen SC3 such that the operator isallowed to change each positive pattern by a drop-down menu method. Theoperator is allowed to change at least one of “typical pattern G1R2F1”,“minor pattern G1R1F2”, “9q deletion pattern G2R1F1”, or “9q⋅22qdeletion pattern G1R1F1” to another pattern by operating the positivepattern selection screen SC3.

In the above-described configuration, at least one of the selectedbright point patterns is changed according to the instruction from theoperator. Therefore, at least one of the selected bright point patternscan be optionally changed.

The processing unit 11 manages, for each operator, an authority tooperate the positive pattern selection screen SC3 on which at least onepositive pattern can be selected. For example, the processing unit 11causes the storage unit 12 to store identification information of theselection screen SC3 and identification information of the operator soas to associate the information with each other. The processing unit 11may cause the display unit 13 to display the positive pattern selectionscreen SC3 associated with a specific operator who has the authority,with reference to the information stored in the storage unit 12.

In the above-described configuration, the specific operator having theauthority is allowed to operate the positive pattern selection screenSC3 associated with the specific operator. Therefore, another operatoris prohibited from operating the positive pattern selection screen SC3and changing the positive pattern which has been desirably set by thespecific operator without permission.

FIG. 5A illustrates one example of a reading process of reading a codeon a storage box in which a labeling reagent is stored, with the use ofa reading unit according to the embodiment. FIG. 5B illustrates oneexample of a reading process of reading a code on an attached documentregarding the labeling reagent, with the use of a reading unit accordingto the embodiment. As shown in FIGS. 5A and 5B, the fluorescence imageanalyzer 1 shown in FIG. 1 may further include a reading unit R forreading a code C on a storage box B in which the labeling reagent isstored, or on an attached document D regarding the labeling reagent. Theobtaining unit 21 of the processing unit 11 shown in FIG. 3 obtainsinformation included in the code C having been read by the reading unitR. The information included in the code C includes, for example,information regarding the probe name (labeling reagent), and at leastone of the positive pattern or the negative pattern associated with theprobe name.

The code C may be a bar code that is a one-dimensional code, or mayinclude a QR code (registered trademark) that is a two-dimensional code,or another code.

FIG. 6 illustrates one example of a registration screen RC1 forregistering information regarding a bright point pattern, on the displayunit 13, according to the embodiment. As shown in FIG. 6 , when the codeC includes information regarding a new bright point pattern, theprocessing unit 11 causes the display unit 13 to display theregistration screen RC1 for registering the information regarding thenew bright point pattern. For example, as shown in FIGS. 5A and 5B, thereading unit R reads the code C on the storage box B in which a labelingreagent is stored, or the document D regarding the labeling reagent. Theprocessing unit 11 refers to information, which is previously stored inthe storage unit 12, such as the information regarding the probe name(labeling reagent) and information regarding at least one of thepositive pattern or the negative pattern associated with the probe name.When the code C includes information other than the information which ispreviously stored in the storage unit 12, the processing unit 11 causesthe display unit 13 to display the registration screen RC1 such that theoperator is allowed to register the information regarding the new brightpoint pattern.

In the example shown in FIG. 6 , the information regarding contents (forexample, “measurement item”, “probe name”, “negative pattern name”,“bright point information” for “negative pattern name”, “positivepattern name”, and “bright point information” for “positive patternname”) to be registered has been already inputted. However, in general,when the registration screen RC1 is displayed, the information has notbeen inputted yet, and the operator registers (for example, manually)each item with reference to the contents, to be registered, on theattached document D shown in FIG. 5B. For the contents to be registered,in the attached document D regarding a labeling reagent manufactured bya company other than SYSMEX CORPORATION or a commercially availablelabeling reagent, for example, a labeled position, and a positivepattern and a negative pattern in using the labeling reagent arewritten. Meanwhile, the code attached for the labeling reagentmanufactured by SYSMEX CORPORATION includes information regarding thecontents to be registered. When the information is read by the readingunit R, the information regarding the contents to be registered may beautomatically registered in the registration screen RC1. The contents tobe registered in the registration screen RC1 may be optionally edited byan operator or may be managed so as to be edited only by an operatorhaving the authority as in the positive pattern selection screen SC3shown in FIG. 4B.

In the above-described configuration, the reading unit R reads the codeC on the storage box B in which the labeling reagent is stored or on thedocument D regarding the labeling reagent. When the code C having beenread includes information regarding a new bright point pattern, theregistration screen for registering the information regarding the newbright point pattern is displayed on the display unit 13. Therefore, theinformation regarding the new bright point pattern can be assuredly andeasily obtained, and the registration screen for registering theinformation regarding the new bright point pattern can be displayed.

The processing unit 11 may cause the display unit 13 to display theregistration screen RC1 in a predetermined display manner for promptingan operator to register the information regarding the new bright pointpattern. For example, the processing unit 11 is configured such that,when the labeling reagent is manufactured by another company or acommercially available one, the operator manually inputs the informationregarding the contents to be registered as described above. Therefore,for example, “G” representing the first bright point, “R” representingthe second bright point, and “F” representing the third bright point maybe previously displayed since they will be registered commonly into the“bright point information” on the registration screen RC1. Specifically,when the registration screen RC1 is displayed on the display unit 13,the operator may be prompted to register 0, 1, 2, or 3 merely in“(space)” portion by “G R F” being previously displayed in the “brightpoint information” for the “positive pattern name”.

In the above-described configuration, workload on an operator is reducedwhen the operator registers the information regarding the new brightpoint pattern.

Returning to FIG. 3 , the determination unit 25 of the processing unit11 determines what positive pattern, among one or more positive patternsincluded in the selected bright point patterns, corresponds to theobtained bright point pattern, based on the obtained bright pointpattern and the selected bright point patterns.

One example of the determination process will be described below. Adetermination method for determining whether or not a cell is anabnormal cell having chromosomal abnormality will be described as oneexample.

FIG. 7A illustrates an example of arrangement of bright points in anormal cell having no chromosomal abnormality, that is, a bright pointpattern (negative pattern). FIGS. 7B to 7D each illustrate an example ofa bright point pattern (positive pattern) of an abnormal cell. In eachof FIGS. 7A to 7D, each image that overlaps the third image isdisplayed.

As shown in FIG. 7A, when chromosomal abnormality such as translocationof the BCR gene locus and the ABL gene locus does not occur, each geneincludes a pair of alleles which exist independently in one nucleus.Therefore, in the first image, two first bright points are in onenucleus region. In the second image, two second bright points are in onenucleus region. In this case, when the first image and the second imagewhich are taken with the same size are combined so as to overlap eachother, the two first bright points and the two second bright points arein one nucleus region in the composite image so as not to overlap eachother. Therefore, the cell in which the two first bright points and thetwo second bright points are in the nucleus region as shown in FIG. 7A,is recognized as having no chromosomal abnormality, that is, the cell isdetermined as a normal cell that is negative for chromosomalabnormality.

One example of the positive pattern will be described by using anexemplary case where a probe [Cytocell BCR/ABL Translocation, ExtraSignal (ES) Probe (manufactured by SYSMEX CORPORATION)] (hereinafter,may be simply referred to as “ES probe”) of which the target is BCR/ABLfusion gene is used. There are a plurality of types of probes of whichthe targets are each BCR/ABL fusion gene.

FIG. 8A and FIG. 8B each illustrate one example of target portions withwhich a probe is to be hybridized. The BCR gene is at chromosome22q11.22-q11.23, and a probe to be hybridized with the BCR gene locus islabeled with the first fluorescence (for example, green). The ABL geneis at chromosome 9q34.11-q34.12, and a probe to be hybridized with theABL gene locus is labeled with the second fluorescence (for example,red). FIG. 8A illustrates a portion to be bound to the above-describedES probe. FIG. 8B illustrates a portion to be bound to the CytocellBCR/ABL Translocation, Dual Fusion (DF) Probe (SYSMEX CORPORATION, CatNo. LPH007) (hereinafter, may be simply referred to as “DF probe”).

As shown in FIG. 7B, when a part of the ABL gene locus is moved tochromosome 22 by translocation, two first bright points are in thenucleus in the first image, and three second bright points are in thenucleus in the second image. In this case, when the first image and thesecond image are combined, one first bright point, two second brightpoints, and a bright point (fused bright point) of one fourthfluorescence (for example, yellow) in which the first bright point andthe second bright point overlap each other are in one nucleus in thecomposite image. Therefore, in the cell that includes the bright pointsas shown in FIG. 7B, translocation of the BCR gene and the ABL gene hasoccurred. That is, the cell is determined as an abnormal cell that ispositive for chromosomal abnormality.

As shown in FIG. 7C, when a part of the BCR gene locus is moved tochromosome 9 and a part of the ABL gene is moved to chromosome 22 bytranslocation, three first bright points are in the nucleus in the firstimage, and three second bright points are in the nucleus in the secondimage. In this case, when the first image and the second image arecombined, one first bright point, one second bright point, and two fusedbright points at each of which the first bright point and the secondbright point overlap each other are in one nucleus in the compositeimage. Therefore, in the cell that includes the bright points as shownin FIG. 7C, translocation of the BCR gene locus and the ABL gene locushas occurred. That is, the cell is determined as an abnormal cell thatis positive for chromosomal abnormality.

As shown in FIG. 7D, when the ABL gene locus is moved to chromosome 22by translocation, two first bright points are in the nucleus in thefirst image, and two second bright points are in the nucleus in thesecond image. In this case, when the first image and the second imageare combined, one first bright point, one second bright point, and onefused bright point at which the first bright point and the second brightpoint overlap each other are in one nucleus in the composite image.Therefore, in the cell that includes the bright points as shown in FIG.7D, translocation of the BCR gene locus and the ABL gene locus hasoccurred. That is, the cell is determined as an abnormal cell that ispositive for chromosomal abnormality.

As described above, whether or not each cell is an abnormal cell havingchromosomal abnormality can be determined based on the positions and thenumber of the bright points in the composite image in which the firstimage and the second image are combined. Therefore, the processing unit11 counts, for each cell, the number of the bright points at eachposition in the composite image in which the first image and the secondimage are combined, as the bright point pattern of fluorescence in thefluorescence image. That is, the processing unit 11 counts the number ofthe first bright points at positions where the first bright points donot overlap the second bright points, the number of the second brightpoints at positions where the second bright points do not overlap thefirst bright points, and the number of the fused bright points atpositions where the first bright points and the second bright pointsoverlap each other. For example, in FIG. 7D, the bright point patterncan be represented such that the number of the independent first brightpoints is “1”, the number of the independent second bright points is“1”, and the number of the fused bright points each of which includesthe first bright point and the second bright point is “1”.

The first bright point, the second bright point, and the fused brightpoint may be represented by colors. For example, the independent firstbright point may be represented as green (G), the independent secondbright point may be represented as red (R), and the fused bright pointmay be represented as yellow (F). By the number of the bright points foreach of G, R, and F being indicated immediately after G, R, F, thebright point pattern can be represented. For example, in FIG. 7D, thebright point pattern can be represented as “G1R1F1”.

The bright point pattern of fluorescence in the fluorescence image canalso be generated such that the number of the first bright pointsdescribed above is the total number of the first bright points in thefirst image and the number of the second bright points described aboveis the total number of the second bright points in the second image. Forexample, in FIG. 7D, the bright point pattern can be generated such thatthe number of the first bright points in the first image is “2”, thenumber of the second bright points in the second image is “2”, and thenumber of the fused bright points in which the first bright point andthe second bright point overlap each other in the composite image is“1”, and the bright point pattern can be represented as “G2R2F1”. Thisalso indicates the same meaning.

Whether or not the first bright point in the first image and the secondbright point in the second image overlap each other in the compositeimage can be determined according to a proportion of a region in whichthe first bright point and the second bright point overlap each other,for example, according to whether or not a proportion of pixels, among aplurality of pixels included in the first bright point, which arelocated at the same positions (coordinate information (x, y)) aspositions of pixels in the second bright point is greater than athreshold value. Furthermore, whether or not the first bright point inthe first image and the second bright point in the second image overlapeach other in the composite image can also be determined according towhether or not a distance between the center point (position of thepixel at which the intensity of the fluorescence is highest) of thefirst bright point and the center point (position of the pixel at whichthe intensity of fluorescence is highest) of the second bright point isless than a threshold value.

The bright point pattern of fluorescence in the fluorescence imageobtained for each cell may be represented as the number of bright pointsfor each color in the composite image. That is, instead of each imagebeing displayed as a gray scale image, the color of each pixel in thefirst image is displayed by color gradation (RGB value) of green, andthe color of each pixel in the second image is displayed by colorgradation (RGB value) of red, based on the pixel value. When the imagesare combined so as to overlap each other, if the cell is determined asan abnormal cell based on a combination of RGB values of the pixels inthe composite image, the green first bright point, the red second brightpoint, and the yellow fused bright point in which the first bright pointand the second bright point overlap each other are in the nucleusregion. Therefore, also by the number of the bright points for eachcolor being counted as the bright point pattern, whether or not the cellis an abnormal cell can be determined.

As described above, the processing unit 11 determines whether the cellis an abnormal cell or a normal cell, based on the bright point patternobtained for each cell. In the present embodiment, the storage unit 12stores reference patterns (a plurality of bright point patterns,including one or more positive patterns, which are previously associatedwith at least one of the measurement item or the labeling reagent) fordetermining whether the cell is an abnormal cell or a normal cell. Theprocessing unit 11 determines whether or not each cell is an abnormalcell, by comparing the bright point pattern obtained for each cell withthe reference pattern (at least one bright point pattern) selected bythe selection unit 23 from the plurality of the reference patternsstored in the storage unit 12.

The reference pattern includes at least one of a bright point pattern(positive pattern) of fluorescence in the fluorescence image of anabnormal cell having chromosomal abnormality, and a bright point pattern(negative pattern) of fluorescence in the fluorescence image of a normalcell having no chromosomal abnormality, as shown in, for example, FIGS.7A to 7D. In the present embodiment, the reference patterns include boththe bright point pattern (positive pattern) of an abnormal cell and thebright point pattern (negative pattern) of a normal cell.

When the bright point pattern of a cell to be analyzed matches thenegative pattern in the comparison in bright point pattern, theprocessing unit 11 determines that the cell is a normal cell. Meanwhile,when the bright point pattern of the cell to be analyzed does not matchthe negative pattern, the processing unit 11 compares the bright pointpattern with a typical positive pattern. When the bright point patternmatches the typical positive pattern, the processing unit 11 determinesthat the cell is a typical abnormal cell. Meanwhile, when the brightpoint pattern does not match the typical positive pattern, theprocessing unit 11 determines the cell is an atypical abnormal cell. Theprocessing unit 11 repeats the same comparison process for all of thecells to be analyzed, and determines whether each cell is an abnormalcell or a normal cell. The processing unit 11 causes the storage unit 12to store the determination result for each cell.

As described above, in the fluorescence image analyzer 1, the brightpoint patterns which are previously associated with at least one of themeasurement item or the labeling reagent may further include a negativepattern, and the processing unit 11 may determine whether or not thesample 10 corresponds to the negative pattern included in the selectedbright point patterns, based on the obtained bright point pattern andthe selected bright point patterns.

In the above-described configuration, not only the positive pattern butalso the negative pattern included in the selected bright point patternscan be further referred to. Therefore, accuracy for determining whetheror not the cell included in the sample is abnormal can be furtherimproved.

Returning to FIG. 3 , the display control unit 27 of the processing unit11 controls the display unit 13 so as to display various screensthereon. The various screens include, for example, the specifying screenSC1 shown in FIG. 4A, the positive pattern selection screen SC3 shown inFIG. 4B, the registration screen RC1 shown in FIG. 6 , and adetermination result screen RC3 described below with reference to FIG. 9.

FIG. 9 illustrates one example of the determination result screen RC3 onthe display unit 13 according to the embodiment. As shown in FIG. 9 ,the display control unit 27 causes the display unit 13 to displayinformation regarding a determination result for each analyzed cell. Theprocessing unit 11 causes the display unit 13 to display, for example, afluorescence image (composite image of the first image, the secondimage, and the third image) of a cell determined as an abnormal cell,and a fluorescence image (composite image of the first image, the secondimage, and the third image) of a cell determined as a normal cell, asthe information regarding the determination result.

On the determination result screen RC3 shown in FIG. 9 , fluorescenceimages are aligned and displayed horizontally and vertically for eachcell, among cells to be analyzed, detected based on a predeterminedanalyzing method. On the determination result screen RC3, a measurementitem 33 used for analyzing the cell is displayed, and an analyzingmethod selection box 34 that allows an analyzing method to be selectedis displayed. On the analyzing method selection box 34, whether or not aDF pattern is to be detected in the analyzing method for a normal cellcan be determined. On the analyzing method selection box 34, forexample, whether a typical abnormal cell (ES major pattern) or anatypical abnormal cell (ES minor pattern, ES deletion pattern) is to bedetected in the analyzing method for an abnormal cell can be determined.The determination result screen RC3 includes a display image selectionbox 38 for allowing selection from among an option for displaying afluorescence image of a cell determined as an abnormal cell (positive),an option for displaying a fluorescence image of a cell determined as anormal cell (negative), and an option for displaying fluorescence imagesof all the analyzed cells, in a drop-down menu method, for the celldetected based on the analyzing method selected in the analyzing methodselection box 34.

The processing unit 11 operates to display a cell fluorescence imageselected in the display image selection box 38 for the cell detectedbased on the analyzing method selected in the analyzing method selectionbox 34, on an image display box 35 of the determination result screenRC3. In the cell fluorescence images displayed in the image display box35, not only a Cell ID but also a determination result indicatingwhether the cell is an abnormal cell (positive) or a normal cell(negative) is displayed for each cell fluorescence image. Thefluorescence image of a cell determined as a normal cell, or thefluorescence images of all the analyzed cells may be displayed accordingto the selection in the display image selection box 38.

Thus, an operator or the like is allowed to observe the fluorescenceimage of the cell determined as an abnormal cell on the display unit 13.When the cell determined as an abnormal cell is determined as a normalcell according to the observation by the operator or the like, theprocessing unit 11 revises, to a normal cell, the determination resultfor the abnormal cell that is selected by the operator or the like as anormal cell through the input unit 14 from among the fluorescence imagesof the abnormal cells displayed on the display unit 13, and that isrevised by a revision button (“Revise Judgement”) 36. The processingunit 11 causes the storage unit 12 to store the revised determinationresult. Similarly, when the cell determined as a normal cell isdetermined as an abnormal cell according to observation by an observersuch as the operator, the processing unit 11 revises, to an abnormalcell, the determination result for the normal cell that is selected bythe operator or the like as an abnormal cell through the input unit 14from among the fluorescence images of the normal cells displayed on thedisplay unit 13, and that is revised by the revision button 36. Theprocessing unit 11 causes the storage unit 12 to store the reviseddetermination result. Thus, accuracy for determining whether the cell isan abnormal cell or a normal cell can be improved. The processing unit11 can also cause the display unit 13 to display again the fluorescenceimage of the cell revised as an abnormal cell or a normal cell.

Thus, the processing unit 11 causes the display unit 13 to display thedetermination result screen RC3 including a result of determining whatpositive pattern, among one or more positive patterns included in thebright point patterns, corresponds to the obtained bright point pattern.

In the above-described configuration, the operator is allowed to easilyrecognize the determination result.

The processing unit 11 generates the information regarding thedetermination result of the sample 10, based on the determination resultof determining whether or not each cell is an abnormal cell. Forexample, the processing unit 11 performs a process of generatinginformation of at least one of the number of abnormal cells, aproportion of the abnormal cells, the number of normal cells, or aproportion of the normal cells, based on the analysis result by theanalyzing method selected in the analyzing method selection box 34. Theproportion of the number of abnormal cells and the proportion of thenumber of normal cells may be, for example, proportions relative to thenumber of all the detected cells (the sum of the number of cellsdetermined as abnormal cells and the number of cells determined asnormal cells) or may be proportions relative to the total number of theanalyzed cells.

The processing unit 11 causes the storage unit 12 to store informationof at least one of the number of abnormal cells, the proportion of theabnormal cells, the number of normal cells, or the proportion of thenormal cells, and causes the display unit 13 to display the information.In one example of the determination result screen RC3 shown in FIG. 9 ,a determination result box 37 is provided, and the number and proportionof cells determined as abnormal cells and the number and proportion ofcells determined as normal cells are displayed in the determinationresult box 37. In this example, the number and proportion of typicalabnormal cells (positive major) determined as “G2R3F1”, the number andproportion of typical abnormal cells (positive minor) determined as“G3R3F3”, the number and proportion of atypical abnormal cells (positiveatypical) determined as “G2R2F1”, and the number and proportion ofnormal cells (negative) determined as “G2R2F0” are displayed in thedetermination result box 37. Other than this, for example, when theanalyzing method for detecting an atypical abnormal cell (ES minorpattern, ES deletion pattern) is selected in the analyzing methodselection box 34, the number and proportion of cells determined asatypical abnormal cells (positive) and the number and proportion ofcells determined as normal cells (negative) may be displayed in thedetermination result box 37.

As indicated in the determination result box 37 shown in FIG. 9 , theprocessing unit 11 causes the display unit 13 to display information ofat least one of the number of abnormal cells included in the sample 10,the proportion of the abnormal cells, the number of normal cellsincluded in the sample 10, or the proportion of the normal cells.

In the above-described configuration, an operator is allowed to easilyrecognize the information of at least one of the number of abnormalcells included in the sample 10, the proportion of the abnormal cells,the number of normal cells included in the sample 10, or the proportionof the normal cells.

As indicated in the image display box 35 and the determination resultbox 37 shown in FIG. 9 , the processing unit 11 causes the display unit13 to display the information of at least one of the number of abnormalcells included in the sample 10, the proportion of the abnormal cells,the number of normal cells included in the sample 10, or the proportionof the normal cells, together with the fluorescence images of the cellsincluded in the sample 10.

In the above-described configuration, an operator is allowed to confirminformation of at least one of the number of abnormal cells included inthe sample 10, the proportion of the abnormal cells, the number ofnormal cells included in the sample 10, or the proportion of the normalcells, together with the fluorescence images of the cells included inthe sample 10.

As indicated in the determination result box 37 shown in FIG. 9 , theprocessing unit 11 may cause the display unit 13 to display thedetermination result regarding a positive pattern (for example, typicalabnormal cell (positive major)) for which the number of abnormal cellsor the proportion of abnormal cells is greatest, in a display mannerdifferent from that for the determination result regarding otherpositive patterns. For example, the information regarding the positivepattern for which the number of abnormal cells or the proportion ofabnormal cells is greatest, may be displayed in red, and the informationregarding the other bright point patterns may be displayed in black. Theinformation regarding the positive pattern for which the number ofabnormal cells or the proportion of abnormal cells is greatest may behighlighted. The information regarding the positive pattern for whichthe number of abnormal cells or the proportion of abnormal cells isgreatest may be indicated as bold characters.

In the above-described configuration, an operator is allowed to moreeasily recognize the determination result regarding the positive patternfor which the number of abnormal cells or the proportion of abnormalcells is greatest, on the determination result screen RC3 includingvarious determination results.

The processing unit 11 may generate, as the information regarding thedetermination result for the sample 10, various other information suchas text information indicating, for example, “may be positive” or “maybe negative”, and cause the display unit 13 to display the otherinformation.

FIG. 10 is an enlarged view of a part of the determination result screenRC3 shown in FIG. 9 . As shown in FIG. 9 and FIG. 10 , the processingunit 11 may cause the display unit 13 to display the determinationresult screen RC3 that includes a graph display box 32 in which theinformation regarding the determination result is represented as agraph. As shown in FIG. 10 , a circle graph for “Type” indicates aproportion of each of typical abnormal cells, atypical abnormal cells,and normal cells, a circle graph for “Nega/Posi” indicates a proportionbetween the abnormal cells and the normal cells, and a circle graph for“Positive” indicates a proportion between typical abnormal cells andatypical abnormal cells.

As shown in FIG. 9 and FIG. 10 , the processing unit 11 may cause thedisplay unit 13 to display a graph image indicating at least one of theproportion of abnormal cells included in the sample 10 or the proportionof normal cells included in the sample 10, together with textinformation indicating at least one of the proportion of the abnormalcells included in the sample 10 or the proportion of the normal cellsincluded in the sample 10. The information may be indicated by anothergraph such as a bar graph other than a circle graph.

In the above-described configuration, an operator is allowed to confirmthe text information indicating at least one of the proportion ofabnormal cells included in the sample 10 or the proportion of normalcells included in the sample 10, together with the graph image. Theoperator is allowed to confirm the graph image, and is thus allowed toeasily recognize the proportion of abnormal cells or the proportion ofnormal cells.

One example of a fluorescence image analyzing method that is executed bythe processing unit 11 based on a computer program that specifies aprocedure of analyzing a fluorescence image of a cell will be describedbelow with reference to FIG. 11 . FIG. 11 is a flow chart showing oneexample of an operation performed by the processing unit of thefluorescence image analyzer, according to the embodiment. The computerprogram is previously stored in the storage unit 12 shown in FIG. 1 .However, the computer program may be installed from, for example, aportable computer-readable storage medium (not shown) such as a CD-ROM,or may be downloaded and installed from, for example, an external server(not shown) via a network (not shown).

As shown in FIG. 11 , for example, the processing unit 11 obtains thefirst to the third images by subjecting images of raw data taken by theimaging unit 160 to gradation inversion and representing the images asgray scale images (step S1). The processing unit 11 obtains a brightpoint pattern of fluorescence in a fluorescence image (step S3). Theprocessing unit 11 causes the display unit 13 to display one or morepositive patterns that are previously associated with at least one ofthe measurement item or the labeling reagent (step S5). The processingunit 11 causes the display unit 13 to display the determination resultfor the sample 10 based on the obtained bright point pattern and thepositive patterns (step S7). Hereinafter, step S3 will be described indetail with reference to FIG. 12 , step S5 will be described in detailwith reference to FIG. 13 , and step S7 will be described in detail withreference to FIG. 14 to FIG. 16 .

FIG. 12 is a flow chart showing one example of a process performed bythe processing unit of the fluorescence image analyzer for obtaining abright point pattern, according to an embodiment. As shown in FIG. 12 ,when the third image has been obtained as indicated at the left end inFIG. 2B, the obtaining unit 21 shown in FIG. 3 generates a graph ofbrightness against frequency based on the brightness in each pixel inthe third image as indicated at the center in FIG. 2B (step S31). Whenthe first image has been obtained as indicated at the left end in FIG.2C, the obtaining unit 21 generates a graph of brightness againstfrequency based on the brightness in each pixel in the first image asindicated at the center in FIG. 2C (step S33). When the second image hasbeen obtained as indicated at the left end in FIG. 2D, the obtainingunit 21 generates a graph of brightness against frequency based on thebrightness in each pixel in the second image as indicated at the centerin FIG. 2D, similarly to the first image (step S35). The obtaining unit21 extracts a region of a nucleus from the third image, and extractsregions of bright points from the bright points in the first image andthe second image (step S37). The obtaining unit 21 generates a brightpoint pattern based on the extracted region of the nucleus and theextracted regions of the bright points (step S39).

FIG. 13 is a flow chart showing one example of a process performed bythe processing unit of the fluorescence image analyzer for selecting abright point pattern, according to the embodiment. As shown in FIG. 13 ,the display control unit 27 shown in FIG. 3 causes the display unit 13to display the specifying screen SC1 (see FIG. 4A) for specifying ameasurement item and a labeling reagent (step S51). An operatorspecifies the measurement item in the specifying screen SC1 displayed onthe display unit 13 (step S53). After the measurement item has beenspecified, the display control unit 27 causes the display unit 13 todisplay the specifying screen SC1 such that a probe name correspondingto the contents of the specified measurement item can be specified (stepS55). The operator specifies the probe name in the specifying screen SC1displayed on the display unit 13 (step S57). The selection unit 23selects positive patterns associated with the specified measurement itemand probe name. The display unit 13 displays the positive patterns (stepS59).

FIG. 14 is a flow chart showing one example of the determination processperformed by the processing unit of the fluorescence image analyzer,according to the embodiment. As shown in FIG. 14 , the selection unit 23shown in FIG. 3 selects a reference pattern (at least one bright pointpattern) from a plurality of reference patterns stored in the storageunit 12 (step S71). When the bright point pattern of a cell to beanalyzed matches a negative pattern in the comparison in the brightpoint pattern, the determination by the determination unit 25 is Yes instep S72, and the process proceeds to step S73, in which thedetermination unit 25 determines that the cell is a normal cell.Meanwhile, when the bright point pattern of the cell to be analyzed doesnot match the negative pattern, the determination by the determinationunit 25 is No in step S72, the process proceeds to step S74, and thebright point pattern of the cell to be analyzed is compared with atypical positive pattern. When the bright point pattern of the cell tobe analyzed matches the typical positive pattern, the determination bythe determination unit 25 is Yes in step S74, and the process proceedsto step S75, in which the determination unit 25 determines that the cellis a typical abnormal cell. Meanwhile, when the bright point pattern ofthe cell to be analyzed does not match the typical positive pattern, thedetermination by the determination unit 25 is No in step S74, and theprocess proceeds to step S76, in which the determination unit 25determines that the cell is an atypical abnormal cell. The determinationunit 25 repeats the same comparison process for all the cells to beanalyzed, and determines whether each cell is an abnormal cell or anormal cell. The determination unit 25 causes the storage unit 12 tostore the determination result for each cell.

FIG. 15 is a flow chart showing one example of the determination processperformed by the processing unit of the fluorescence image analyzer,according to the embodiment. The determination process shown in FIG. 15is different from the determination process shown in FIG. 14 in thatwhether or not the bright point pattern of a cell to be analyzed matchesa positive pattern is firstly determined in the determination processshown in FIG. 15 whereas whether or not the bright point pattern of acell to be analyzed matches a negative pattern is firstly determined inthe determination process shown in FIG. 14 . As shown in FIG. 15 , theselection unit 23 shown in FIG. 3 selects a reference pattern (at leastone bright point pattern) from a plurality of reference patterns storedin the storage unit 12 (step S81). When the bright point pattern of acell to be analyzed matches a typical positive pattern in the comparisonin the bright point pattern, the determination by the determination unit25 is Yes in step S82, and the process proceeds to step S83, in whichthe determination unit 25 determines that the cell is a typical abnormalcell. Meanwhile, when the bright point pattern of the cell to beanalyzed does not match the typical positive pattern, the determinationby the determination unit 25 is No in step S82, the process proceeds tostep S84, and the determination unit 25 compares the bright pointpattern of the cell to be analyzed with an atypical positive pattern.When the bright point pattern of the cell to be analyzed matches theatypical positive pattern, the determination by the determination unit25 is Yes in step S84, and the process proceeds to step S86, in whichthe determination unit 25 determines that the cell is an atypicalabnormal cell. Meanwhile, when the bright point pattern of the cell tobe analyzed does not match the atypical positive pattern, thedetermination by the determination unit 25 is No in step S84, and theprocess proceeds to step S85, in which the determination unit 25determines that the cell is a normal cell. The determination unit 25repeats the same comparison process for all the cells to be analyzed,and determines whether each cell is an abnormal cell or a normal cell.The determination unit 25 causes the storage unit 12 to store thedetermination result for each cell.

In the determination process shown in FIG. 14 and FIG. 15 , the numberof the negative patterns may be plural. That is, when whether or not thebright point pattern of a cell to be analyzed matches a negative patternis determined, the bright point pattern of the cell to be analyzed maybe compared with a plurality of different negative patterns.Furthermore, in FIG. 14 and FIG. 15 , when the bright point pattern of acell to be analyzed does not match any of the positive patterns havingbeen referred to or when the bright point pattern of a cell to beanalyzed does not match any of the negative patterns having beenreferred to, information indicating that an error has occurred may bedisplayed on the display unit 13. Furthermore, in FIG. 14 and FIG. 15 ,when the bright point pattern of a cell to be analyzed does not matchany of the positive patterns having been referred to or when the brightpoint pattern of a cell to be analyzed does not match any of thenegative patterns having been referred to, other positive patterns orother negative patterns which are not included in the patterns to bereferred to may be read from the storage unit 12, and the bright pointpattern of the cell to be analyzed may be compared with the otherpositive patterns or the other negative patterns.

FIG. 16 is a flow chart showing one example of a display control processperformed by the processing unit of the fluorescence image analyzer,according to the embodiment. As shown in FIG. 16 , the display controlunit 27 shown in FIG. 3 obtains the determination result from thedetermination unit 25 or the storage unit 12 (step S91). The displaycontrol unit 27 generates display information for displaying thedetermination result on the display unit 13, and outputs the generateddisplay information to the display unit 13 (step S93). The display unit13 displays the determination result screen RC3 shown in FIG. 9 based onthe received display information (step S95).

As described above, according to the above-described embodiment, thefluorescence image analyzer 1 obtains a bright point pattern offluorescence in a fluorescence image, and causes the display unit 13 todisplay a plurality of positive patterns that are previously associatedwith at least one of a measurement item or a labeling reagent, andcauses the display unit 13 to display a determination result for thesample 10 based on the obtained bright point pattern and the positivepatterns. Therefore, what positive pattern, among a plurality ofpositive patterns, corresponds to a cell included in the sample 10 canbe inhibited from being undetermined. Accordingly, accuracy fordetermining whether the sample 10 is positive or negative can beimproved.

Other Embodiments

The above-described embodiments are for allowing the present disclosureto be easily understood, and are not restrictive. The present disclosurecan be changed/modified (for example, the embodiments may be combined,or a part of the structure of each embodiment may be omitted) withoutdeparting from the gist of the present disclosure and the presentdisclosure also includes its equivalents.

What is claimed is:
 1. A fluorescence image analyzer for analyzing afluorescence image of cells contained in a sample, the fluorescenceimage analyzer comprising: a light source configured to apply light tothe sample; an image capture device having a light receiving surface andconfigured to capture a fluorescence image of the cells by whichfluorescence is generated by applying the light; a processor programmedto: process the captured fluorescence image; and a display, wherein theprocessor is programmed to: obtain a bright point pattern offluorescence in the captured fluorescence image; cause the display todisplay a list of different possible positive patterns, the listcorresponding to at least one of a specified measurement item or aspecified labeling reagent, receive, as a selection from the list, atleast one of the different possible positive patterns; and cause thedisplay to display information of at least one of an abnormal cell countin the sample or a proportion of abnormal cells in the sample, based onthe obtained bright point pattern and the selection from the list of atleast one of the plurality of different possible positive patterns. 2.The fluorescence image analyzer of claim 1, wherein the processor causesthe display to display the list of different possible positive patterns,and check boxes arranged so as to provide user selection with arespective check box of different possible positive patterns from thelist.
 3. The fluorescence image analyzer of claim 1, wherein theprocessor is programmed to: manage, for each user, an authority for aparticular user to operate a selection screen corresponding to thatparticular user that allows selection from among the list of differentpossible positive patterns; and cause the display to display theselection screen corresponding to the particular user having theauthority.
 4. The fluorescence image analyzer of claim 1, furthercomprising a memory configured to store a determination result for thecells included in the sample, wherein the processor causes the displayto display the stored determination result.
 5. The fluorescence imageanalyzer of claim 1, wherein the processor causes the display to displayinformation of at least one of the abnormal cell count in the sample orthe proportion of the abnormal cells in the sample, together with thefluorescence image of the cells.
 6. The fluorescence image analyzer ofclaim 1, wherein the processor causes the display to display a graphimage indicating the proportion of the abnormal cells in the sample,together with text information indicating the proportion of the abnormalcells in the sample.
 7. The fluorescence image analyzer of claim 1,wherein the processor causes the display to display a determinationresult regarding a positive pattern for which the abnormal cell count isgreatest, or the proportion of the abnormal cell is greatest, in adisplay manner different from that for a determination result regardinganother positive pattern.
 8. The fluorescence image analyzer of claim 1,wherein the different possible positive patterns are determined based ona color and a number of bright points of florescence.
 9. Thefluorescence image analyzer of claim 1, wherein the different possiblepositive patterns include a typical positive pattern and an atypicalpositive pattern.
 10. The fluorescence image analyzer of claim 1,wherein the processor is further programmed to receive at least one of aselection of the specified measurement item indicative of a type ofmeasurement or a selection of the specified labeling reagent indicativeof a probe, and the list of different possible positive patterns aremade available for selection based on the selection of at least one ofthe specified measurement item or the selection of the specifiedlabeling reagent.
 11. The fluorescence image analyzer of claim 1,wherein the list of different possible positive patterns include atleast one of a typical positive pattern, an atypical positive pattern,or a minor positive pattern, the abnormal cells include at least one oftypical abnormal cells, atypical abnormal cells, or minor abnormalcells, and the processor is programmed to cause the display to displayinformation of at least one of a count of the typical abnormal cells inthe sample as the abnormal cell count, a proportion of the typicalabnormal cells in the sample as the proportion of abnormal cells, acount of the atypical abnormal cells in the sample as the abnormal cellcount, a proportion of the atypical abnormal cells in the sample as theproportion of abnormal cells, a count of the minor abnormal cells in thesample as the abnormal cell count, or a proportion of the minor abnormalcells in the sample as the proportion of abnormal cells based on theobtained bright point pattern and the selection of at least one of thelist of different possible positive patterns.
 12. A fluorescence imageanalyzing method for analyzing a fluorescence image of cells containedin a sample, the method comprising: capturing a fluorescence image ofthe cells by which fluorescence is generated by applying light to thesample; and processing the captured fluorescence image, wherein theprocessing comprises: obtaining a bright point pattern of fluorescencein the fluorescence image; displaying a list of different possiblepositive patterns, the list corresponding to at least one of a specifiedmeasurement item or a specified labeling reagent; receiving as aselection from the list at least one of the different possible positivepatterns; and displaying information of at least one of an abnormal cellcount in the sample or a proportion of abnormal cells in the sample,based on the obtained bright point pattern and the selection from thelist of at least one of the different possible positive patterns. 13.The fluorescence image analyzing method of claim 12, wherein thedisplaying the list of different possible positive patterns comprisesdisplaying the list of different possible positive patterns, and checkboxes arranged so as to provide user selection with a respective checkbox of different possible positive patterns from the list.
 14. Thefluorescence image analyzing method of claim 12, wherein the processingcomprises: managing, for each user, an authority for a particular userto operate a selection screen corresponding to that particular user thatallows selection from among the list of different possible positivepatterns; and displaying the selection screen corresponding to theparticular user having the authority.
 15. The fluorescence imageanalyzing method of claim 12, further comprising storing a determinationresult for the cells included in the sample, wherein the processingcomprises displaying the stored determination result.
 16. Thefluorescence image analyzing method of claim 12, wherein the displayingthe information of at least one of the abnormal cell count in the sampleor the proportion of the abnormal cells in the sample, comprisesdisplaying the information together with the fluorescence image of thecells.
 17. The fluorescence image analyzing method of claim 12, whereinthe displaying the information of at least one of the abnormal cellcount in the sample or the proportion of the abnormal cells in thesample comprises displaying a graph image indicating the proportion ofthe abnormal cells in the sample together with text informationindicating the proportion of the abnormal cells in the sample.
 18. Thefluorescence image analyzing method of claim 12, wherein the processingcomprises displaying a determination result regarding a positive patternfor which the abnormal cells count in the sample is greatest, or theproportion of the abnormal cells in the sample is greatest, in a displaymanner different from that for a determination result regarding anotherpositive pattern.
 19. The fluorescence image analyzing method of claim12, wherein the list of different possible positive patterns aredetermined based on a color and a number of bright point of florescence.20. The fluorescence image analyzing method of claim 12, wherein thelist of different possible positive patterns include a typical positivepattern and an atypical positive pattern.
 21. The fluorescence imageanalyzing method of claim 12, further comprising receiving at least oneof a selection of the specified measurement item indicative of a type ofmeasurement or a selection of the specified labeling reagent indicativeof a probe, and making the list of different possible positive patternsavailable for selection based on the selection of at least one of thespecified measurement item or the selection of the specified labelingreagent.